Simultaneous screening and quantitation of 18 antihistamine drugs in blood by liquid chromatography ionspray tandem mass spectrometry
Simultaneous screening and quantitation of 18 antihistamine drugs in blood by liquid chromatography ionspray tandem mass spectrometry
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DOI：
10.1016/s0379-0738(01)00460-1
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发表时间：
2001-09-15
影响因子：
2.2
通讯作者：
Vuori, E
中科院分区：
文献类型：
--
作者：
Gergov, M;Robson, JN;Vuori, E
建立了液相色谱-串联质谱法（LC-MS/MS）同时检测血液中18种抗组胺药物的方法。样品预处理涉及碱性抗组胺药的液-液萃取，然后是酸性抗组胺药的第二次萃取。碱性药物的回收率为43 - 113%，酸性药物的回收率为23 - 66%。在C-18反相柱上使用乙腈-乙酸铵移动的相（pH 3.2）通过LC运行合并的提取物。用三级四极杆质量分析仪进行质谱分析。使用多反应监测（MRM）进行筛选，然后在随后的MS/MS运行中通过其产物离子光谱自动验证任何暂时鉴定为抗组胺药物的化合物。在验证试验中，该方法在相关浓度下显示出良好的线性。血液中达到的定量限在0.0005和0.01 mg/l之间变化，低于治疗浓度（C-max）。除氯马斯汀在血液中的浓度极低外，通过产物离子光谱进行鉴别的限度也低于C-max。测定内相对标准偏差优于10%，左卡巴斯汀的不准确度为39%，赛克力嗪的不准确度为5%，大多数值为
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is presented for the simultaneous screening and quantitation of 18 antihistamine drugs in blood samples. Sample pretreatment involved liquid-liquid extraction of the basic antihistamines followed by a second extraction of the acidic antihistamines. The recoveries were 43-113% for basic drugs and 23-66% for acidic drugs. The combined extracts were run by LC on C-18 reversed phase column using acetonitrile-ammonium acetate mobile phase at pH 3.2. The mass spectrometric analysis was performed with a triple stage quadrupole mass analyzer. Screening was performed using Multiple reaction monitoring (MRM) and any compounds tentatively identified as, antihistamine drugs were then automatedly verified by their Product Ion Spectra in a subsequent MS/MS run.Quantitation was based on the MRM data from the screening step. In validation tests, the method showed good linearity at the relevant concentrations. The attained limits of quantitation varied between 0.0005 and 0.01 mg/l in blood and were lower than the therapeutic concentrations (C-max). The limits for identification by Product Ion Spectra were also lower than C-max, except for clemastine, which has exceptionally low concentrations in blood. The intra-assay relative standard deviations were better than 10% and the inaccuracy varied between 39% for levocabastine and 5% for cyclizine, the majority of the values being